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The activity of frontal motor areas during hand-object interaction is coordinated by dense communication along specific white matter pathways. This architecture allows the continuous shaping of voluntary motor output but, despite extensive investigation in non-human primate studies, remains poorly understood in humans. Disclosure of this system is crucial for predicting and treatment of motor deficits after brain lesions. For this purpose, we investigated the effect of direct electrical stimulation on white matter pathways within the frontal lobe on hand-object manipulation. This was tested in 34 patients (15 left hemisphere, mean age 42 years, 17 male, 15 with tractography) undergoing awake neurosurgery for frontal lobe tumour removal with the aid of the brain mapping technique. The stimulation outcome was quantified based on hand-muscle activity required by task execution. The white matter pathways responsive to stimulation with an interference on muscles were identified by means of probabilistic density estimation of stimulated sites, tract-based lesion-symptom (disconnectome) analysis and diffusion tractography on the single patient level. Finally, we assessed the effect of permanent tract disconnection on motor outcome in the immediate postoperative period using a multivariate lesion-symptom mapping approach. The analysis showed that stimulation disrupted hand-muscle activity during task execution at 66 sites within the white matter below dorsal and ventral premotor regions. Two different EMG interference patterns associated with different structural architectures emerged: (i) an ‘arrest’ pattern, characterized by complete impairment of muscle activity associated with an abrupt task interruption, occurred when stimulating a white matter area below the dorsal premotor region. Local middle U-shaped fibres, superior fronto-striatal, corticospinal and dorsal fronto-parietal fibres intersected with this region. (ii) a ‘clumsy’ pattern, characterized by partial disruption of muscle activity associated with movement slowdown and/or uncoordinated finger movements, occurred when stimulating a white matter area below the ventral premotor region. Ventral fronto-parietal and inferior fronto-striatal tracts intersected with this region. Finally, only resections partially including the dorsal white matter region surrounding the supplementary motor area were associated with transient upper-limb deficit (P = 0.05; 5000 permutations). Overall, the results identify two distinct frontal white matter regions possibly mediating different aspects of hand-object interaction via distinct sets of structural connectivity. We suggest the dorsal region, associated with arrest pattern and postoperative immediate motor deficits, to be functionally proximal to motor output implementation, while the ventral region may be involved in sensorimotor integration required for task execution.

The cortical area within the human primary motor cortex (M1) that hosts the representation of the hand and fingers is known as the 'hand-knob' and is essential for voluntary hand movement. The anatomo-functional heterogeneity described within the monkey primary motor cortex (M1) in a rostro-caudal direction suggests an internal subdivision in two sectors originating different systems of connections to the spinal cord. Direct investigation of the human hand-knob has been prevented, so far, by methodological constraints. The unique setting of brain tumour resection with the brain mapping technique in awake patients enables direct electrophysiological investigation of the functional properties of the human hand-knob. Motor-evoked potentials (MEPs) elicited by Direct Electrical Stimulation (DES) at high frequency (HF-DES) delivered along the hand-knob in rostro-caudal direction, i.e., from the central to the precentral sulcus, were recorded from the hand/arm muscles in patients at rest. The sites located near the precentral sulcus identified with HF-DES were then stimulated with low-frequency DES (LF-DES) during a hand manipulation task (HMt) to assess whether DES affected task execution. From the stimulated sites, corticofugal projections and U-shaped tracts connecting with adjacent gyri were traced using diffusion tensor and spherical deconvolution tractography. Analysis of MEPs showed a rostro-caudal gradient of cortical excitability along the hand-knob (the rostral sector being less excitable). Stimulation of rostral sites during the HMt impaired the task by inducing dysfunctional recruitment or, alternatively, suppression of distal muscles. Diffusion tractography showed different patterns of rostro-caudal connectivity for the U-shaped tracts. Overall data suggests, in humans, the anatomo-functional subdivision of the human hand-knob in two sectors, possibly subserving different roles in motor control.

Fine motor skills rely on the control of hand muscles exerted by a region of primary motor cortex (M1) that has been extensively investigated in monkeys. Although neuroimaging enables the exploration of this system also in humans, indirect measurements of brain activity prevent causal definitions of hand motor representations, which can be achieved using data obtained during brain mapping in tumor patients. High-frequency direct electrical stimulation delivered at rest (HF-DES-Rest) on the hand-knob region of the precentral gyrus has identified two sectors showing differences in cortical excitability. Using quantitative analysis of motor output elicited with HF DES-Rest, we characterized two sectors based on their excitability, higher in the posterior and lower in the anterior sector. We studied whether the different cortical excitability of these two regions reflected differences in functional connectivity (FC) and structural connectivity (SC). Using healthy adults from the Human Connectome Project (HCP), we computed FC and SC of the anterior and the posterior hand-knob sectors identified within a large cohort of patients. The comparison of FC of the two seeds showed that the anterior hand-knob, relative to the posterior hand-knob, showed stronger functional connections with a bilateral set of parietofrontal areas responsible for integrating perceptual and cognitive hand-related sensorimotor processes necessary for goal-related actions. This was reflected in different patterns of SC between the two sectors. Our results suggest that the human hand-knob is a functionally and structurally heterogeneous region organized along a motor-cognitive gradient.SIGNIFICANCE STATEMENTThe capability to perform complex manipulative tasks is one of the major characteristics of primates and relies on the fine control of hand muscles exerted by a highly specialized region of the precentral gyrus, often termed the “hand-knob” sector. Using intraoperative brain mapping, we identify two hand-knob sectors (posterior and anterior) characterized by differences in cortical excitability. Based on resting-state functional connectivity (FC) and tractography in healthy subjects, we show that posterior and anterior hand-knob sectors differ in their functional connectivity (FC) and structural connectivity (SC) with frontoparietal regions. Thus, anteroposterior differences in cortical excitability are paralleled by differences in FC and SC that likely reflect a motor (posterior) to cognitive (anterior) organization of this cortical region.

We present an integrated additive manufacturing approach for the rapid prototyping of objects with embedded electric circuits. Our approach relies on the combined use of standard fused filament fabrication (FFF) for the production of thermoplastic 3D freeform components, and supersonic cluster beam deposition (SCBD) for the fabrication of embedded electrical conducting lines and resistors with tailored conductivity. SCBD is an additive fabrication technique based on the deposition of neutral metallic clusters carried in a highly collimated supersonic beam. SCBD produces strongly adherent conducting layers onto polymeric substrates with electrical resistance depending only on the thickness of the cluster-assembled film. A multi-step fabrication procedure alternating FFF and SCBD was developed and optimized allowing the fabrication of conductive 3D oblique paths, bridging vias, and sockets for standard electronic components fitting. This resulted in the simplification of the topology of planar electric circuits by enabling out-of-plane connections, minimizing the implementation of bulky passive electrical components and avoiding the use of soldering and conductive adhesives for the integration of active electronic components. A dark-activated light sensor was produced as a demonstrator.

A key aspect of cognitive control is the management of conflicting incoming information to achieve a goal, termed 'interference control'. Although the role of the right frontal lobe in interference control is evident, the white matter tracts subserving this cognitive process remain unclear. To investigate this, we studied the effect of transient network disruption (by means of direct electrical stimulation) and permanent disconnection (resulting from neurosurgical resection) on interference control processes, using the Stroop test in the intraoperative and extraoperative neurosurgical setting. We evaluated the sites at which errors could be produced by direct electrical stimulation during an intraoperative Stroop test in 34 patients with frontal right hemisphere glioma. Lesion-symptom mapping was used to evaluate the relationship between the resection cavities and postoperative performance on the Stroop test of this group compared with an additional 29 control patients who did not perform the intraoperative test (63 patients in total aged 17-77 years; 28 female). We then examined tract disruption and disconnection in a subset of eight patients who underwent both the intraoperative Stroop test and high angular resolution diffusion imaging (HARDI) tractography. The results showed that, intraoperatively, the majority of sites associated with errors during Stroop test performance and concurrent subcortical stimulation clustered in a region of white matter medial to the right inferior frontal gyrus, lateral and superior to the striatum. Patients who underwent the intraoperative test maintained cognitive control ability at the 1-month follow-up (P = 0.003). Lesion-symptom analysis showed resection of the right inferior frontal gyrus was associated with slower postoperative Stroop test ability (corrected for multiple comparisons, 5000 permutations). The stimulation sites associated with intraoperative errors most commonly corresponded with the inferior fronto-striatal tracts and anterior thalamic radiation (over 75% of patients), although the latter was commonly resected without postoperative deficits on the Stroop test (in 60% of patients). Our results show converging evidence to support a critical role for the inferior frontal gyrus in interference control processes. The intraoperative data combined with tractography suggests that cortico-subcortical tracts, over cortico-cortical connections, may be vital in maintaining efficiency of cognitive control processes. This suggests the importance of their preservation during resection of right frontal tumours.

A key aspect of cognitive control is the management of conflicting incoming information to achieve a goal, termed 'interference control'. Although the role of the right frontal lobe in interference control is evident, the white matter tracts subserving this cognitive process remain unclear. To investigate this, we studied the effect of transient network disruption (by means of direct electrical stimulation) and permanent disconnection (resulting from neurosurgical resection) on interference control processes, using the Stroop test in the intraoperative and extraoperative neurosurgical setting. We evaluated the sites at which errors could be produced by direct electrical stimulation during an intraoperative Stroop test in 34 patients with frontal right hemisphere glioma. Lesion-symptom mapping was used to evaluate the relationship between the resection cavities and postoperative performance on the Stroop test of this group compared with an additional 29 control patients who did not perform the intraoperative test (63 patients in total aged 17-77 years; 28 female). We then examined tract disruption and disconnection in a subset of eight patients who underwent both the intraoperative Stroop test and high angular resolution diffusion imaging (HARDI) tractography. The results showed that, intraoperatively, the majority of sites associated with errors during Stroop test performance and concurrent subcortical stimulation clustered in a region of white matter medial to the right inferior frontal gyrus, lateral and superior to the striatum. Patients who underwent the intraoperative test maintained cognitive control ability at the 1-month follow-up (P = 0.003). Lesion-symptom analysis showed resection of the right inferior frontal gyrus was associated with slower postoperative Stroop test ability (corrected for multiple comparisons, 5000 permutations). The stimulation sites associated with intraoperative errors most commonly corresponded with the inferior fronto-striatal tracts and anterior thalamic radiation (over 75% of patients), although the latter was commonly resected without postoperative deficits on the Stroop test (in 60% of patients). Our results show converging evidence to support a critical role for the inferior frontal gyrus in interference control processes. The intraoperative data combined with tractography suggests that cortico-subcortical tracts, over cortico-cortical connections, may be vital in maintaining efficiency of cognitive control processes. This suggests the importance of their preservation during resection of right frontal tumours.

Dorsal and ventral premotor (dPM and vPM) areas are crucial in control of hand muscles during object manipulation, although their respective role in humans is still debated. In patients undergoing awake surgery for brain tumors, we studied the effect of direct electrical stimulation (DES) of the premotor cortex on the execution of a hand manipulation task (HMt). A quantitative analysis of the activity of extrinsic and intrinsic hand muscles recorded during and in absence of DES was performed. Results showed that DES applied to premotor areas significantly impaired HMt execution, affecting task-related muscle activity with specific features related to the stimulated area. Stimulation of dorsal vPM induced both a complete task arrest and clumsy task execution, characterized by general muscle suppression. Stimulation of ventrocaudal dPM evoked a complete task arrest mainly due to a dysfunctional recruitment of hand muscles engaged in task execution. These results suggest that vPM and dPM contribute differently to the control of hand muscles during object manipulation. Stimulation of both areas showed a significant impact on motor output, although the different effects suggest a stronger relationship of dPM with the corticomotoneuronal circuit promoting muscle recruitment and a role for vPM in supporting sensorimotor integration.

A thermally shrinkable and conductive nanocomposite material is prepared by supersonic cluster beam implantation (SCBI) of neutral Au nanoparticles (Au NPs) into a commercially available thermo-retractable polystyrene (PS) sheet. Micronanowrinkling is obtained during shrinking, which is studied by means of SEM, TEM and AFM imaging. Characteristic periodicity is determined and correlated with nanoparticle implantation dose, which permits us to tune the topographic pattern. Remarkable differences emerged with respect to the well-known case of wrinkling of bilayer metal-polymer. Wrinkled composite surfaces are characterized by a peculiar multiscale structuring that promises potential technological applications in the field of catalytic surfaces, sensors, biointerfaces, and optics, among others.

Electroactive ionic gel/metal nanocomposites are produced by implanting supersonically accelerated neutral gold nanoparticles into a novel chemically crosslinked ion conductive soft polymer. The ionic gel consists of chemically crosslinked poly(acrylic acid) and polyacrylonitrile networks, blended with halloysite nanoclays and imidazolium-based ionic liquid. The material exhibits mechanical properties similar to that of elastomers (Young's modulus ≈ 0.35 MPa) together with high ionic conductivity. The fabrication of thin (≈100 nm thick) nanostructured compliant electrodes by means of supersonic cluster beam implantation (SCBI) does not significantly alter the mechanical properties of the soft polymer and provides controlled electrical properties and large surface area for ions storage. SCBI is cost effective and suitable for the scaleup manufacturing of electroactive soft actuators. This study reports the high-strain electromechanical actuation performance of the novel ionic gel/metal nanocomposites in a low-voltage regime (from 0.1 to 5 V), with long-term stability up to 76 000 cycles with no electrode delamination or deterioration. The observed behavior is due to both the intrinsic features of the ionic gel (elasticity and ionic transport capability) and the electrical and morphological features of the electrodes, providing low specific resistance (

Supersonic cluster beam implantation of Ag nanoparticles is proposed for the fabrication of stretchable and compliant electrodes for dielectric elastomer actuators (DEAs) with reduced thickness. Thanks to the low-energy and finely tunable implantation process, a nanocomposite Ag/polydimethylsiloxane electrode layer is produced with a moderate stiffening effect for the DEA in contrast with a common deposition strategy for electrodes. Thin DEAs with an overall thickness of 17 μm were fabricated and tested under different preloading conditions, demonstrating a max uniaxial actuation strain of 2.5% at an actuation voltage of 765 V, lower than the typical voltage values of DEAs. The electrodes remained conductive up to 40% strain, and they fully recovered the original resistance after 70% stretching. Our results represent a significant step towards the development of DEAs operating at reduced actuation voltages, by stacking of micrometer-thick elastomer films, paving the way to novel applications in soft robotics.

Paper is a cheap, lightweight and renewable material with increasing applicative interest as a substrate for disposable and flexible electronics. The integration of planar energy storage devices on paper is a necessary and challenging step for the development of smart and autonomous flexible electronic platforms. Here we report the one-step, room temperature, fabrication of planar microsupercapacitors where nanostructured current collectors and carbon electrodes are deposited by supersonic cluster beam deposition (SCBD) on plain paper sheets and 1-Ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl) imide ([Emim][NTf2]) is used as ionic liquid electrolyte. As-prepared microsupercapacitors showed a high capacitance density of about 7 F cm−3 and good capacity retention upon prolonged cycling. The encapsulation of SCBD-made microsupercapacitors by means of a polydimethylsiloxane layer and their usability in driving a low power temperature sensor are demonstrated.

We report the rapid prototyping of passive electrical components (resistors and capacitors) on plain paper by an additive and parallel technology consisting of supersonic cluster beam deposition (SCBD) coupled with shadow mask printing. Cluster-assembled films have a growth mechanism substantially different from that of atom-assembled ones providing the possibility of a fine tuning of their electrical conduction properties around the percolative conduction threshold. Exploiting the precise control on cluster beam intensity and shape typical of SCBD, we produced, in a one-step process, batches of resistors with resistance values spanning a range of two orders of magnitude. Parallel plate capacitors with paper as the dielectric medium were also produced with capacitance in the range of tens of picofarads. Compared to standard deposition technologies, SCBD allows for a very efficient use of raw materials and the rapid production of components with different shape and dimensions while controlling independently the electrical characteristics. Discrete electrical components produced by SCBD are very robust against deformation and bending, and they can be easily assembled to build circuits with desired characteristics. The availability of large batches of these components enables the rapid and cheap prototyping and integration of electrical components on paper as building blocks of more complex systems.

We report a scanning optical spectrometer based on the use of a stretchable elastomeric reflective grating. The grating is obtained by supersonic cluster beam implantation of silver nanoparticles on polydimethylsiloxane previously grooved by molding to create a replica of a commercial digital versatile disk grating. The use of a stretchable grating allows the spectrometer spanning the whole optical wavelength range by solely extending the diffraction element by more than 100% of its original dimensions. The stretchable reflective optical grating shows excellent performances and stability upon thousands of stretching cycles. The use of this elastomeric element makes the optical layout and the mechanics of the spectrometer extremely simple and advantageous for those applications where spectral resolution is not a major requirement. As a proof of principle, we present the absorption spectrum of Rhodamine B in solution obtained by our spectrometer and compared to commercial instruments.